CN101530440A - Oral pharmaceutical preparation of aralia elata total sapogenin and preparation method and application thereof - Google Patents
Oral pharmaceutical preparation of aralia elata total sapogenin and preparation method and application thereof Download PDFInfo
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Abstract
The invention discloses an oral pharmaceutical preparation of aralia elata total sapogenin and a preparation method and application thereof, pertaining to the field of traditional Chinese medicine. In respect of the pharmaceutical preparation, sapogenin compositions in aralia elata are hydrolyzed into sapogenin, then the sapogenin is matched with high-efficiency medical auxiliary materials and mixed evenly by the method of micronization, and then the oral pharmaceutical preparation is produced. The pharmaceutical preparation can enhance the dispersibility, wettability and solubility of the sapogenin compositions, increase the absorption and utilization degree of the sapogenin and improve the biological utilization degree of the sapogenin. The pharmaceutical preparation has outstanding effects in respects of pain easing, anti-inflammatory, antitumor, anti-ageing, liver nourishing, blood fat adjustment and diabetes treatment.
Description
Technical field
The present invention relates to a kind of pharmaceutical preparation that contains Cortex Araliae Elatae Radicis total sapogenins, it is oral drug preparation of main effective ingredient and uses thereof that the saponin component in particularly a kind of Aralia mandshurica is hydrolyzed into sapogenin.Belong to the field of Chinese medicines.
Background technology
Aralia mandshurica (Aralia elata Seem.A.mandshurica Max) is a Wu Jia Ke Cortex araliae chinensis platymiscium, and another name Liao Dong Cortex araliae chinensis, Cortex Araliae Elatae Radicis, japanese angelica tree, tiger sun thorn originate in ground such as China northeast, Korea, Russia, day wood.Record except that wind disease, the tumor of harnessing the river, mend effects such as waist kidney, strengthening bone and muscle according to " wooden careless detailed outline ".Aralia mandshurica is mainly with root bark and bark people medicine, its nature and flavor are arduous, slightly poisonous, effect with invigorating QI and tranquilization, strong smart nourishing kidney, expelling wind and activating blood circulation, removing damp and stopping pain, in order to a little less than treatment neurasthenia, rheumatic arthritis, hepatitis, diabetes, stomach spasm, constipation, traumatic hemorrhage and the yang deficiency gas, disease such as deficiency of kidney-QI.Aralia mandshurica root and Ye Zhongjun contain triterpene saponin, and main active is oleanolic acid type and Folium Vaccinii vitis-idaeae acid type triterpene saponin, and its aglycon is oleanolic acid and ursolic acid.Pharmacological research shows that the Aralia mandshurica total saponins has oxygen lack resistant function; improve the mouse anti stress ability, promote the phagocytic function of mononuclear phagocyte, the function of interrenal system is had facilitation; expeirmental myocardial ischemia there are stronger protective effect, anti-aging effects etc.
Though it is more that the Aralia mandshurica total saponins has been used, prior art has all been ignored the research to its aglycon, and its effect and applicable cases are in space state always.
Summary of the invention
It is the oral drugs of active component with the Cortex Araliae Elatae Radicis total sapogenins that first purpose of the present invention is to provide a kind of;
Second purpose provides the dosage form of this medicine, particularly a kind of high-efficiency preparation;
The 3rd purpose provides the preparation method of this medicine high-efficiency preparation.
Provide at last that this medicine is used for easing pain in preparation, antiinflammatory, antitumor, defying age, the application that protects the liver, transfer the medicine of blood fat or treatment diabetes.
The object of the invention first purpose is achieved in that
The inventor provides a kind of oral medicine, and this medicine is active component with the Cortex Araliae Elatae Radicis total sapogenins.
Although what people took is the preparation that contains the Aralia mandshurica total saponins in the past, must wait until that saponin is become aglycon by the intestinal microbial population decomposition and inversion after, could real onset.And the many defectives that exist in this conversion process cause the drug effect shakiness: medicine long operational time, transformation efficiency in vivo is low; Conversion process is uncertain, decomposes the aglycon of being not only that obtains, and also may be other inert matters; Individual variation is big, and everyone transformation efficiency height is different, can not give full play to drug effect or the like.In view of above reason, have only and Cortex Araliae Elatae Radicis total sapogenins is directly made pharmaceutical preparation be applied to human body, when could guarantee to reduce dosage, improve drug effect.
Medical value at Aralia mandshurica, the inventor extracts from the Aralia mandshurica medical material by prior art and obtains the Aralia mandshurica total saponins, and it is hydrolyzed, make saponin component wherein slough glycosyl, generation has more bioactive sapogenin, promptly becomes Cortex Araliae Elatae Radicis total sapogenins provided by the present invention.The inventor confirms that after deliberation glycoside material gained aglycon after hydrolysis has not had glycosyl, and its lipotropy strengthens greatly, thereby aglycon is absorbed than the easier intestinal mucosa that sees through of glycosides; Simultaneously, the molecule of medicine is more little also easy more to be absorbed, the glycosides hydrolysis fall with glycan molecule become aglycon after, molecular change gets littler, also can easier absorption.In addition, directly as medical substance, overcome in the past glycoside material long operational time, factor such as transformation efficiency is low, conversion results is uncertain in vivo, improved the bioavailability of medicine greatly, saved drug resource with aglycon.
The Cortex Araliae Elatae Radicis total sapogenins can use separately in medicine provided by the invention, also can unite use with the other drug composition, that is: in active constituents of medicine, can have only the pure product of Cortex Araliae Elatae Radicis total sapogenins, also can be the Cortex Araliae Elatae Radicis total sapogenins crude product, can also be the mixture of Cortex Araliae Elatae Radicis total sapogenins and other drug, reaches the purpose of partner treatment, auxiliary treatment.The present invention preferably uses the Cortex Araliae Elatae Radicis total sapogenins crude product, promptly extracts the Aralia mandshurica total saponins from medical material, hydrolysis in a suitable manner again, and make with extra care as required, obtain required purity.Except mainly containing the Cortex Araliae Elatae Radicis total sapogenins, also contain inevitable accessory substance and impurity in other extractions and the hydrolytic process in extract obtained, comprise a small amount of unhydrolysed glycosides and secondary glycosides etc.
Above-mentioned method for hydrolysis has comprised acid hydrolysis, enzyme hydrolysis or microbial hydrolysis, and the inventor is through screening, and following several concrete method for hydrolysis is provided respectively: acid hydrolysis can be hydrolyzed with hydrochloric acid, sulphuric acid, acetic acid and the formic acid etc. of 1～10mol/L; Enzyme hydrolysis can be hydrolyzed with emulsin, maltase, conversion carbohydrase, hesperidinase etc.; Microorganism can be hydrolyzed with escherichia coli, enterococcus, lactobacillus, clostridium, lopsided thalline, bifidus bacillus and human body intestinal canal normal flora etc.
Second purpose of the present invention provides the pharmaceutical preparation of above-mentioned Cortex Araliae Elatae Radicis total sapogenins, especially a kind of high-efficiency preparation.Those skilled in the art can cooperate Cortex Araliae Elatae Radicis total sapogenins of the present invention with suitable adjuvant easily, are prepared into various conventional formulations.But the inventor is also noted that another problem, and promptly because aglycon fat-soluble stronger relatively, thereby after its preparation was applied to human body, aglycon composition wherein was difficult for wetted and stripping, if can not address this problem, also can influence the absorption of aglycon.So at this problem, the inventor provides a kind of new solution, can guarantee Cortex Araliae Elatae Radicis total sapogenins is made high-efficiency preparation, this technical scheme is:
Scheme one: a kind of is the efficient pharmaceutical preparation of active component with Cortex Araliae Elatae Radicis total sapogenins of the present invention, contain bio-adhesive agent and wetting agent in its adjuvant, can also contain the conventional adjuvant on dispersant and other pharmaceuticss, and be made into oral formulations such as tablet, capsule, granule, pill.
The core of this technical scheme is Cortex Araliae Elatae Radicis total sapogenins is used for pharmaceutical preparation, and guarantees the efficient utilization of Cortex Araliae Elatae Radicis total sapogenins by special adjuvant.Thereby; embody in the concrete pharmaceutical preparation; can have only Cortex Araliae Elatae Radicis total sapogenins of the present invention in its active constituents of medicine; also can be used with other medicinal or non-medical substances; as long as its objective is contained Cortex Araliae Elatae Radicis total sapogenins is utilized bio-adhesive agent and wetting agent, can also utilize dispersant, carry out moistening, dispersion; to make oral high-efficiency preparation, all should be in the scope of the present patent application protection.In like manner, technical solution of the present invention is selected bio-adhesive agent and wetting agent for use, can also be with dispersant as main adjuvant, and purpose is to make Cortex Araliae Elatae Radicis total sapogenins to be able to fully, to disperse uniformly, is beneficial to absorption; In actual applications; can also add other conventional adjuvants and molding adjuvant as required; as starch, microcrystalline Cellulose, carboxymethylstach sodium, citric acid, sodium bicarbonate, low-substituted hydroxypropyl methylcellulose, lactose, mannitol, citric acid, Aspartane, dextrin, magnesium stearate etc.; these all should be considered as the work finished on the basis of the technology of the present invention, also should be subjected to the protection of the present patent application.
In this technical scheme, the bio-adhesive agent is preferably chitosan, carbomer, polyvinylpyrrolidone or the mixture between them; Wetting agent is preferably lecithin, poloxamer or its mixture; Dispersant is preferably micropowder silica gel, cyclodextrin, Polyethylene Glycol or the mixture between them.
Wherein, chitosan, carbomer have the bio-adhesive performance as the bio-adhesive agent, but prolong drug significantly improves bioavailability of medicament in the gastrointestinal holdup time.Surfactant such as lecithin, poloxamer has the effect of moistened surface to Cortex Araliae Elatae Radicis total sapogenins, reduces surface tension, increases the dissolubility of fat-soluble Cortex Araliae Elatae Radicis total sapogenins, promotes it to absorb rapidly, is beneficial to rapid performance curative effect.Micropowder silica gel, cyclodextrin, Polyethylene Glycol be as dispersant, and itself possess hydrophilic property is beneficial to moistening, the dispersion of aglycon, strengthens stability of drug.Cortex Araliae Elatae Radicis total sapogenins of the present invention and above-mentioned adjuvant are used, and fully mix homogeneously can strengthen wherein dispersibility, the wettability of Cortex Araliae Elatae Radicis total sapogenins, improves its bioavailability.
In the preferred case, each composition proportion is preferably active component 20～60% in the medicine of the present invention, bio-adhesive agent 1～10%, wetting agent 5～20%, dispersant 0～30%, other adjuvants 0～50%.Other adjuvants wherein are meant other adjuvants of preparation some in forming process, as: starch, microcrystalline Cellulose, carboxymethylstach sodium, citric acid, sodium bicarbonate, low-substituted hydroxypropyl methylcellulose, lactose, mannitol, citric acid, Aspartane, dextrin, magnesium stearate etc.
Technique scheme is mainly used in oral formulations, and optimum dosage form is tablet, capsule, granule, powder and pill.
Scheme two: a kind of is the efficient pharmaceutical preparation of active component with Cortex Araliae Elatae Radicis total sapogenins of the present invention, contain dispersant and wetting agent in its adjuvant, can also contain the conventional adjuvant on bio-adhesive agent and other pharmaceuticss, and oral formulations such as the soft capsule that is made into, liquid hard capsule, drop pill.
The core of this technical scheme is Cortex Araliae Elatae Radicis total sapogenins is used for pharmaceutical preparation, and guarantees the efficient utilization of Cortex Araliae Elatae Radicis total sapogenins by special adjuvant.Thereby; embody in the concrete pharmaceutical preparation; can have only Cortex Araliae Elatae Radicis total sapogenins of the present invention in its active constituents of medicine; also can be used with other medicinal or non-medical substances; as long as its objective is contained Cortex Araliae Elatae Radicis total sapogenins is utilized dispersant and wetting agent, can also utilize the bio-adhesive agent, carry out moistening, dispersion; to make oral high-efficiency preparation, all should be in the scope of the present patent application protection.In like manner, technical solution of the present invention is selected dispersant and wetting agent for use, can also be with the bio-adhesive agent as main adjuvant, and purpose is to make Cortex Araliae Elatae Radicis total sapogenins to be able to fully, to disperse uniformly, is beneficial to absorption; In actual applications; can also add other conventional adjuvants and molding adjuvant as required; as glycerol, glycine, citric acid, ethyl hydroxybenzoate, Cera Flava etc., these all should be considered as the work finished on the basis of the technology of the present invention, also should be subjected to the protection of the present patent application.
In this technical scheme, dispersant is preferably vegetable oil or Polyethylene Glycol; Wetting agent is preferably lecithin, poloxamer, propylene glycol or the mixture between them; The bio-adhesive agent is preferably chitosan, carbomer or its mixture.Sapogenin and above-mentioned adjuvant are used, and fully mix homogeneously can strengthen aglycon dispersibility, wettability, improves its bioavailability.
Wherein, surfactants such as lecithin, poloxamer, propylene glycol have the effect of moistened surface to Cortex Araliae Elatae Radicis total sapogenins, reduce surface tension, increase the dissolubility of fat-soluble Cortex Araliae Elatae Radicis total sapogenins, promote it to absorb rapidly, be beneficial to rapid performance curative effect.Vegetable oil, Polyethylene Glycol can be uniformly dispersed Cortex Araliae Elatae Radicis total sapogenins as dispersant.Chitosan, carbomer have the bio-adhesive performance as the bio-adhesive agent, but prolong drug significantly improves bioavailability of medicament in the gastrointestinal holdup time.Cortex Araliae Elatae Radicis total sapogenins of the present invention and above-mentioned adjuvant are used, and fully mix homogeneously can strengthen wherein dispersibility, the wettability of Cortex Araliae Elatae Radicis total sapogenins, improves its bioavailability.
In the preferred case, each composition proportion is preferably active component 10～40% in the medicine of the present invention, bio-adhesive agent 0～10%, wetting agent 5～20%, dispersant 50～80%, other adjuvants 0～20%.Other adjuvants wherein are meant other adjuvants of preparation some in forming process, as: glycerol, glycine, citric acid, ethyl hydroxybenzoate, Cera Flava etc.
Technique scheme is mainly used in oral formulations, and optimum dosage form is liquid hard capsule, soft capsule and drop pill.
The 3rd purpose of the present invention provides the preparation method of above-mentioned high-efficiency preparation, core technology wherein is with behind Cortex Araliae Elatae Radicis total sapogenins and any method mix homogeneously during required adjuvant mixes by fusion, dissolving, stirring, grinding or micronizing, add required conventional formulation adjuvant again, technology is made preparation routinely.And the blended method of the preferred vibromill micronizing of the mixed method here.
Have only by effective hybrid mode, could guarantee that contained Cortex Araliae Elatae Radicis total sapogenins and special adjuvant fully are uniformly dispersed in the extract, moistening rapidly, stripping, absorption when being applied to human body, performance is effect efficiently.Through inventor's checking, modes such as fusion, dissolving, stirring, grinding or micronizing mixing can both realize the object of the invention, and micronizing mode effect wherein are the most outstanding.
Though superfine communication technique occurs already, the application in technical field of Chinese medicines stays in the conceptive of " pulverizing " always, do not break through all the time, thereby its scope is limited to very much.The inventor finds in practice, superfine communication technique has been not only crushing technology, a kind of especially high efficient mixed technology, it can make aglycon be subjected to intensive forward extrusion power and the tangentially effect of shearing force with adjuvant, utilization at a high speed, high-energy is pulverized, mix, resulting powder medium particle diameter is reduced to below the 10 μ m by 75 original μ m, the granularity exquisiteness, evenly, surface area increases, porosity increases, drug particle is fully contacted with the adjuvant particle, mix, both improved the dispersion of drug particle, guaranteed its rapid moistening and stripping again, improved the absorbance and the bioavailability of medicine greatly, its advantage is that present conventional mixed method is incomparable.At this wherein, vibromill micronizing mode is to realize the best approach of the object of the invention.
Medicine of the present invention can be used for easing pain in preparation, antiinflammatory, antitumor, defying age, protect the liver, transfer the medicine of blood fat or treatment diabetes to use.
Beneficial effect
Technical scheme of the present invention considers that from practical angle in conjunction with the needs of preparation, after the saponin component hydrolysis in the Rhizoma Dioscoreae, the Rhizoma Dioscoreae total sapogenins of gained adds proper auxiliary materials, pulverizes by the method height of micronizing and mixes, and makes required preparation.Can make the maximum moistening of active component, dissolving and absorption, can prolong the holdup time of aglycon again, further promote absorbing of aglycon, improve bioavailability.Specifically, this patent method has following advantage:
1, improves bioavailability: adopt this patent invention preparation method, can obviously improve the deficiency of additive method, it has following clear superiority: the poorly water-soluble of aglycon, lipotropy is strong, being difficult for moistening absorbs, and the present invention has added hydrophilic high-molecular biologic binder and wetting agent, dispersant before the preparation micropowder mixes, strengthened the wettability of aglycon, being beneficial to it absorbs, and the rest parts saponin component is beneficial to moistening after the hydrolysis, also can certain wettability be arranged to lipophilic aglycon; Micronization itself can strengthen the performance of sticking of medicine greatly, improves wettability, and the present invention added the high-performance bio binder, can prolong the holdup time of micropowder, strengthens the absorption of effective ingredient.
2, conservation, increase operation rate: the inventive method can maximally utilise crude drug, uses the curative effect that can obtain former prescription less than the dose of general preparation, economizes in raw materials, and improves the utilization rate of crude drug, can reduce the waste of resource again.
So the present invention has obtained outstanding technique effect, has reached goal of the invention.For further checking the present invention in order to prove that pharmaceutical preparation of the present invention improves the effect of bioavailability, the inventor cures mainly according to its function, has carried out animal contrast pharmacodynamic experiment:
One, Cortex Araliae Elatae Radicis total sapogenins is to the antiinflammatory action research of mice
1, material
1.1 animal
Animal: Kunming mouse, male.Provide by Shandong University's Experimental Animal Center.
1.2 medicine
The saponin preparation: get Aralia mandshurica total saponins 46g (being equivalent to Aralia mandshurica medical material 1kg), add carbomer 10g, lecithin 15g, and add micropowder silica gel to 100g, micronizing 60 minutes, getting wherein, 30g is suspended to 100ml with water;
The general preparation of sapogenin: get Cortex Araliae Elatae Radicis total sapogenins 41g (being equivalent to Aralia mandshurica medical material 1kg), add starch to 100g, mixing, getting wherein, 30g is suspended to 100ml with water;
The sapogenin high-efficiency preparation: get Cortex Araliae Elatae Radicis total sapogenins 41g (being equivalent to Aralia mandshurica medical material 1kg), add carbomer 10g, lecithin 15g, and add micropowder silica gel to 100g, micronizing 60 minutes, getting wherein, 30g is suspended to 100ml with water.
Positive control drug: get dexamethasone 6g, be suspended to 100ml with water.
2, method and result
2.1 experimental technique is got the mice of 50 body weight 25g ± 2g, evenly be divided into 5 groups at random, blank group, aglycon high-efficiency preparation group, the general preparation group of aglycon, saponin preparation group, positive controls, except that the blank group, irritate stomach every day and give corresponding medicine 0.2ml/10g, the blank group is irritated stomach and is given the equal-volume normal saline, once a day, and successive administration 3 days.60min after the last administration, each treated animal is applied to auricle two sides, a mice left side with dimethylbenzene 50ul and causes inflammation, cuts ears after causing scorching 30min, and hammer is got ears same area auricle, weighs, and is calculated as follows swelling degree and inhibitory rate of intumesce.
Swelling degree=cause inflammation pick up the ears sheet heavy-it is non-that to cause the inflammation sheet of picking up the ears heavy
Inhibitory rate of intumesce=(matched group swelling degree-administration group swelling degree)/matched group swelling degree
2.2 experimental result the results are shown in following table.
The influence of table xylol induced mice ear swelling (X ± S)
Annotate: each administration group and matched group are relatively.
*P<0.05，
**P<0.01。
Above result of the test shows that Aralia mandshurica total aglycones high-efficiency preparation group can significantly reduce dimethylbenzene induced mice ear thickness, relatively has utmost point significant difference with matched group, and effective than saponin preparation group.The general preparation group of aglycon effect is better than saponin preparation group.
Two, the antitumor action of Aralia mandshurica total aglycones test
1, material
1.1 experimental animal
S
180The tumor ascites mice of going down to posterity is available from the institute of oncology, Jilin Province; Kunming mouse, the SPF level, Anhui Province's Experimental Animal Center provides, credit number: SCXK (Anhui) 2005-0001 number.
1.2 medicine
The preparation method of saponin preparation, the general preparation of sapogenin, sapogenin high-efficiency preparation is the same.
Positive control drug: get cyclophosphamide 2g, add the solution that water is made 100ml.
2, method and result
2.1 test method is got Kunming mouse, is divided into 5 groups at random, 10 every group, is respectively blank group, positive drug group, aglycon high-efficiency preparation group, the general preparation group of aglycon, saponin preparation group.Chose transplantation tumor 7 days, tumor growth is good, the tangible ascites of the abdominal tympanites mice of going down to posterity, the skin of abdomen sterilization, thrust the abdominal cavity with disposable sterilized hemostix through stomach wall, extraction ascites is put into aseptic beaker and is diluted to 1: 3 cancerous cell suspension with normal saline, in right oxter inoculation 0.2ml of every test of each group Kunming mouse.Each is organized mice and begins to irritate every day stomach next day in inoculated tumour and give corresponding medicine 0.25ml/10g, and the blank group is irritated stomach and given the equal-volume normal saline, successive administration 30 days.Administration finishes next day, and each group test mice is put to death, and separates subcutaneous lump and weighs, and respectively organizes the tumor growth situation, and makes t check, comparable group differences significance.
2.2 the result of the test experimental result sees the following form.
Table 1 pair mice (inoculation S
180) tumor growth influence (X ± S, n=10)
Annotate: compare with matched group,
*P＜0.05,
*P＜0.01.
Above-mentioned result of the test shows that Cortex Araliae Elatae Radicis total sapogenins high-efficiency preparation group and positive drug group have obvious antineoplastic, to S
180The tumour inhibiting rate of mice transplanted tumor is higher, compares with the blank group, has utmost point significant difference; The general preparation group of aglycon, saponin preparation group and matched group relatively have significant difference, and the effect of the general preparation group of aglycon are better than saponin preparation group.
Three, Cortex Araliae Elatae Radicis total sapogenins is to CCl
4The protective effect of acute liver damage
1, material
1.1 animal
Kunming mouse, male and female half and half.Provide by Peking University's Experimental Animal Center.
1.2 medicine
The preparation method of saponin preparation, the general preparation of sapogenin, sapogenin high-efficiency preparation is the same.
1.3 reagent
CCl
4, chemical reagent three factories in Tianjin produce.
2, method and result
2.1 experimental technique is got 50 of mices, male and female half and half, and body weight 20 ± 2g evenly is divided into 5 groups at random, i.e. normal saline group, model group, aglycon high-efficiency preparation group, the general preparation group of aglycon, saponin preparation group.Except that normal saline group, model group, each group is all irritated stomach and is given respective sample, and dosage is 0.3ml/10g, normal saline group, model group are irritated stomach and are given the equal-volume normal saline, administration every day 1 time, successive administration 5 days, in the 5th day except that the blank group, every group of lumbar injection CCl
4(20ul/kg), get hematometry serum paddy transaminase (ALT) and glutamic oxaloacetic transaminase, GOT (AST) after 16 hours, and hepatic tissue is made the conventional organization pathological examination.
2.2 experimental result the results are shown in following table.
Table is to CCl
4The ALT of hepatic injury and the influence of AST (X ± S)
Compare with model group,
*P＜0.05,
*P＜0.01.
Above result of the test shows that aglycon high-efficiency preparation group can reduce ALT and the AST level in the serum preferably, and the variation and the necrosis that alleviate hepatic tissue relatively have utmost point significant difference with the blank group; The general preparation group of aglycon effect slightly is better than saponin preparation group.
Four, Cortex Araliae Elatae Radicis total sapogenins is to the influence of aging model learning and memory of little mouse
1, material
1.1 animal
Kunming mouse, male, provide by Peking University's Experimental Animal Center.
1.2 medicine
The preparation method of saponin preparation, the general preparation of sapogenin, sapogenin high-efficiency preparation is the same.
2, method and result
2.1 experimental technique is got 50 of healthy mices, is divided into 5 groups at random: blank group, model group, the general preparation group of aglycon, aglycon high-efficiency preparation group, saponin preparation group.Except that the blank group, difference subcutaneous injection 5%D-galactose, 0.25ml/10g; The isopyknic normal saline of blank group subcutaneous injection; Every day 1 time, continuous 6 weeks.Modeling administration is simultaneously irritated stomach and is given corresponding test sample 0.25ml/10g, and blank group and model group are irritated stomach and given the equal-volume normal saline; Behind last administration and the injection of d-galactose 2h, animal is put into diving tower case endoadaptation 3min, logical immediately then 36V alternating current, animal is shocked by electricity.Its normal reaction is that the rebound platform is to hide noxious stimulation.So train 5min, the test of reforming behind the 24h.This promptly remembers the maintenance test.The record mice jumps off the incubation period of platform and the errors number in the 5min for the 1st time.
2.2 test results test the results are shown in following table.
Table is to the influence of aging model learning and memory of little mouse (X ± S)
Annotate: compare with model group,
*P＜0.05,
*P＜0.01.
Experimental result shows, compares with the blank group, and the model group mouse memory obviously fails, and showing as errors number increases, and shorten incubation period, the modeling success.Compare with model group, aglycon high-efficiency preparation group, the general preparation group of aglycon can make mouse wrong times obviously reduce, and obviously prolong incubation period, has utmost point significant difference, all is better than saponin preparation group.
Five, Cortex Araliae Elatae Radicis total sapogenins paratartaric acid antimony potassium causes the influence of mouse writhing reaction
1, material
1.1 the animal Kunming mouse is provided by Shandong University's Experimental Animal Center.
1.2 medicine and reagent
The preparation method of saponin preparation, the general preparation of sapogenin, sapogenin high-efficiency preparation is the same.
Reagent: antimony potassium tartrate.
2, method and result
2.1 test method is got 40 of mices, male and female half and half, body weight 20 ± 2g, evenly be divided into 4 groups at random, every group 10, promptly blank group, sapogenin high-efficiency preparation group, the general preparation group of sapogenin, saponin preparation group, gastric infusion dosage is 20ml/kg, blank group filling stomach gives the normal saline with volume, administration every day 1 time, successive administration 5 days, 1h after last 1 administration, the antimony potassium tartrate liquid of the new preparation of every Mus lumbar injection is observed incubation period and the interior mouse writhing generation number of 10min that writhing response appears in mice first immediately.
2.2 result of the test the results are shown in following table.
The influence of table paratartaric acid antimony potassium induced mice writhing response (X ± S)
Annotate: with blank group ratio,
*P＜0.05,
*P＜0.01.
Above result of the test shows that sapogenin high-efficiency preparation group can obviously prolong the incubation period that mice is turned round body first, reduces the mouse writhing number of times, relatively has utmost point significant difference with the blank group; The general preparation group of sapogenin, saponin preparation group and blank group relatively have significant difference, and the general preparation group of sapogenin effect is better than saponin preparation group.
Six, Cortex Araliae Elatae Radicis total sapogenins is to the influence of hyperlipidemia rats serum TC, TG, HDL-C
1, material
1.1 animal Wistar rat is provided by Shandong University's Experimental Animal Center.
1.2 medicine and reagent
The preparation method of saponin preparation, the general preparation of sapogenin, sapogenin high-efficiency preparation is the same.
Positive control drug: get lovastatin 2g, be suspended to 100ml with water.
HDL-C (HDL-C) testing cassete, T-CHOL (TC) testing cassete, triglyceride (TG) testing cassete.
1.3 instrument ZS-3 type semiautomatic biochemistry analyzer.
2, method and result
2.1 the foundation of animal model 1% cholesterol, 0.2% methylthiouracil, 0.3% cholate, 7.5% Adeps Sus domestica, 10% yolk powder, 81% normal feedstuff is made high lipid food, the feed rat.
2.2 test method rat adaptability was raised 5 days, fasting 12h, detect serum TC and TG, by body weight and blood lipid level rat is divided into 6 groups at random, 10 every group: i.e. blank group, model control group, aglycon high-efficiency preparation group, the general preparation group of aglycon, saponin preparation group, lovastatin group.Except that blank group feed normal feedstuff, all the other each groups are all fed high lipid food, average every Mus 18g every day, and deficiency gives normal diet and replenishes.When giving high lipid food, gastric infusion dosage is 10ml/kg, and blank group and model group filling stomach give the normal saline with volume, administration every day 1 time, successive administration 30 days is after the last administration, fasting 12h, postcava is got blood, enzymatic assays TC, TG, HDL-C.
2.3 result of the test sees the following form to the influence of hyperlipidemia rats serum TC, TG, HDL-C.
Table to the influence of hyperlipidemia rats serum TC, TG, HDL-C (mmol/L, X ± S, n=10)
Annotate: compare with model control group,
*P＜0.05,
*P＜0.01.
Above result of the test shows that TC, TG level are significantly higher than blank group (P＜0.01) in the model control group rat serum, and HDL-C significantly is lower than blank group (P＜0.01), prompting modeling success; Compare with model control group, aglycon high-efficiency preparation group and lovastatin group all can significantly reduce TC, TG, and rising blood HDL-C level; The general preparation group of aglycon, saponin preparation group and model control group relatively can reduce TC, TG, rising blood HDL-C level, and the general preparation group of aglycon effect is better than saponin preparation group.
Seven, Cortex Araliae Elatae Radicis total sapogenins is to the influence of diabetes rat model hyperglycemia
1, material
1.1 animal Wistar rat is provided by Shandong University's Experimental Animal Center.
1.2 medicine and reagent
The preparation method of saponin preparation, the general preparation of sapogenin, sapogenin high-efficiency preparation is the same.
Positive control drug: get glyburide 3g, be suspended to 100ml with water.
1.3 instrument blood sugar analyzer.
2, method and result
2.1 test method is chosen 100 of healthy rats, body weight 200 ± 20g, and male and female half and half, adaptability raised for 1 week, 18 ℃～24 ℃ of room temperatures.Make before the diabetes model behind the fasting 12h, get blood, use blood sugar analyzer to survey blood glucose value from rat tail vein, choose blood glucose value in 5.0mmol/L～6.0mmol/L scope rat with 55mg/kg streptozotocin lumbar injection; Fasting 12h and get blood and survey blood glucose behind the 72h, select 50 of the close rats of blood glucose value, be divided into 5 groups at random: model group, glyburide group, aglycon high-efficiency preparation group, the general preparation group of aglycon, glycosides formulation group, other get blood glucose value in 5.0mmol/L～6.0mmol/L scope 10 of rats as the blank group, each is organized gastric infusion dosage and is 10ml/kg, blank group filling stomach gives the normal saline with volume, administration every day 1 time, continuous 14d, get blood respectively at the 3rd day, the 7th day, the 14th day fasting 12h during the administration, survey blood glucose value.
2.2 test results test the results are shown in following table.
Table to the influence of diabetes rat model hyperglycemia (X ± S, n=10)
Annotate: compare with model group,
*P＜0.05,
*P＜0.01.
Above result of the test shows, behind the 55mg/kg streptozotocin lumbar injection rat blood sugar obviously being raise, and aglycon high-efficiency preparation group and glyburide group, blood glucose obviously reduced in the 7th day, and its blood sugar reducing function was more obvious in the 14th day; The general preparation group of aglycon, the 14th day blood sugar reducing function of saponin preparation group are comparatively obvious.
The specific embodiment
Enumerate embodiment below, further specify the present invention, each embodiment only is used to illustrate the present invention, does not limit the present invention:
Embodiment 1
Get Cortex Araliae Elatae Radicis total sapogenins 100g, add chitosan 20g, carbomer 10g, poloxamer 50g, lecithin 50g, micropowder silica gel 30g, betacyclodextrin 80g, and add starch to 450g, the vibromill micronizing was mixed 30 minutes, granulated drying, granulate is made capsule.
Embodiment 2
Get Cortex Araliae Elatae Radicis total sapogenins 80g, add chitosan 20g, poloxamer 30g, lecithin 10g, micropowder silica gel 30g, betacyclodextrin 20g, microcrystalline Cellulose 50g, and add starch to 300g, vibromill micronizing 30 minutes, adding 70% ethanol closes and sticks together 10 minutes, pill bar, gradation and round, drying, pill is made in polishing.
Embodiment 3
Get Cortex Araliae Elatae Radicis total sapogenins 120g, add chitosan 2g, lecithin 10g, Aspartane 1g, and add dextrin to 200g, stir, dry-pressing is granulated, and granule is made in packing.
Embodiment 4
Get Cortex Araliae Elatae Radicis total sapogenins 60g, add chitosan 10g, polyvinylpyrrolidone 2g, poloxamer 8g, betacyclodextrin 20g, and add starch to 200g, the mix homogeneously that sieves is granulated, and the dress enteric coated capsule is made capsule.
Embodiment 5
Get Cortex Araliae Elatae Radicis total sapogenins 100g, add polyvinylpyrrolidone 10g, poloxamer 20g, lecithin 10g, micropowder silica gel 10g, betacyclodextrin 50g, the vibromill micronizing was mixed 50 minutes, granulates, tabletting, coating is made tablet.
Embodiment 6
Get Cortex Araliae Elatae Radicis total sapogenins 20g, add propylene glycol 10g, poloxamer 10g, lecithin 20g, chitosan 10g, carbomer 10g, add PEG400 to 200g, vibromill micronizing 20 minutes makes mix homogeneously, makes liquid hard capsule, promptly.
Embodiment 7
Get Cortex Araliae Elatae Radicis total sapogenins 30g, add lecithin 10g, glycine 10g, glycerol 30g adds Macrogol 600 again to 200g, and vibromill micronizing 30 minutes makes mix homogeneously, is pressed into soft capsule, promptly.
Embodiment 8
Get Cortex Araliae Elatae Radicis total sapogenins 50g, add chitosan 10g, lecithin 20g, poloxamer 4g, ethyl hydroxybenzoate 1g, Cera Flava 5g, and add soybean oil to 200g, and stirring evenly, colloid mill ground 5 minutes, was pressed into soft capsule, promptly.
Embodiment 9
Get Cortex Araliae Elatae Radicis total sapogenins 40g, propylene glycol 10g, glycerol 5g, polyethylene glycol 6000 50g, Macrogol 4000 50g, heating and melting, mix homogeneously drips and makes drop pill, promptly.
Embodiment 10
Get Cortex Araliae Elatae Radicis total sapogenins 100g, lecithin 25g, ethyl hydroxybenzoate 2.5g, Cera Flava 47.5g, and add soybean oil to 500g, vibromill ultra micro 40 minutes makes mix homogeneously, is pressed into soft capsule, promptly.
Embodiment 11
Get Aralia mandshurica medical material 4kg, pulverize, add 70% ethanol percolation and extract, percolate reclaims ethanol, and water liquid adds 0.5% activated carbon decolorizing, filter, filtrate is crossed the D101 macroporous resin column, respectively water, 20% ethanol, 60% ethanol elution is collected 60% ethanol elution, reclaim ethanol, surplus water liquid emulsin hydrolysis 72 hours, hydrolyzed solution concentrating under reduced pressure, drying under reduced pressure, get Cortex Araliae Elatae Radicis total sapogenins (crude product) 218g, add carbomer 40g, lecithin 40g, micropowder silica gel 40g, and add starch to 400g, micronizing was mixed 60 minutes, granulate, drying, granulate is loaded capsule.
Embodiment 12
Get Aralia mandshurica 3kg, coarse pulverization adds 60% alcohol reflux three times, each 1.5 hours, filter merging filtrate, decompression recycling ethanol, water liquid are added on the D101 macroporous adsorptive resins, respectively with water, 30% ethanol, 70% ethanol elution, collect 70% ethanol elution, decompression recycling ethanol, surplus water liquid was with 2mol/L sulphuric acid hydrolysis 2 hours, and it is an amount of that hydrolyzed solution adds calcium oxide, filter, and with an amount of washing with alcohol precipitation, filter, merge water liquid and ethanol washing liquid, decompression recycling ethanol, drying under reduced pressure gets Cortex Araliae Elatae Radicis total sapogenins (crude product) 173g, adds chitosan 20g, lecithin 20g, micropowder silica gel 100g, and add microcrystalline Cellulose to 400g, micronizing was mixed 50 minutes, granulated drying, granulate, compacting are in flakes.
Embodiment 13
Get Aralia mandshurica 3kg, coarse pulverization adds 70% alcohol reflux three times, each 1.5 hours, filter merging filtrate, decompression recycling ethanol, water liquid extracts three times with water-saturated n-butanol, n-butyl alcohol liquid evaporate to dryness, and dry thing is dissolved in water, 115 ℃ of sterilization 20min, with lactic acid bacteria culturers hydrolysis 72 hours, hydrolyzed solution concentrating under reduced pressure, drying under reduced pressure, get Cortex Araliae Elatae Radicis total sapogenins (crude product) 194g, add carbomer 40g, lecithin 20g, polyethylene glycol 6000 40g, and add dextrin to 400g, micronizing was mixed 80 minutes, granulate, drying, granulate makes granule.
Embodiment 14
Get Aralia mandshurica 4kg, coarse pulverization adds 70% alcohol reflux three times, each 1.5 hours, filter merging filtrate, decompression recycling ethanol, water liquid extracts three times with water-saturated n-butanol, n-butyl alcohol liquid evaporate to dryness, dry thing is dissolved in water, and is added on the D101 macroporous adsorptive resins, respectively with water, 30% ethanol, 80% ethanol elution, collect 80% ethanol elution, decompression recycling ethanol adds hydrochloric acid and makes acid content reach 5mol/L, hydrolysis 3 hours, hydrolyzed solution hydro-oxidation sodium is regulated pH to 7.0, concentrate, drying with the dehydrated alcohol reflux, extract,, reclaims ethanol, drying under reduced pressure, get Cortex Araliae Elatae Radicis total sapogenins 185g, add chitosan 10g, poloxamer 50g, cyclodextrin 180g, carboxymethyl starch sodium 20g, and add starch to 500g, micronizing was mixed 30 minutes, with water is adhesive, and the system soft material is pressed into ball.
Embodiment 15
Get Aralia mandshurica 4kg, coarse pulverization, add 70% alcohol reflux three times, each 1.5 hours, filter, merging filtrate, decompression recycling ethanol, water liquid extracts three times with water-saturated n-butanol, n-butyl alcohol liquid evaporate to dryness, dry thing is dissolved in water, 115 ℃ of sterilization 20min are with bifidus bacillus strain fermentation hydrolysis 72 hours, hydrolyzed solution concentrating under reduced pressure, drying under reduced pressure, Cortex Araliae Elatae Radicis total sapogenins 193g, add chitosan 10g, lecithin 20g, and with soybean oil to 500g, micronizing was mixed 30 minutes, and fill becomes liquid hard capsule.
Embodiment 16
Get Aralia mandshurica 3kg, coarse pulverization adds 70% alcohol reflux three times, each 1.5 hours, filter merging filtrate, decompression recycling ethanol, water liquid extracts three times with water-saturated n-butanol, n-butyl alcohol liquid evaporate to dryness, and dry thing is dissolved in water, be added on the D101 macroporous adsorptive resins, respectively with water, 30% ethanol, 80% ethanol elution is collected 80% ethanol elution, decompression recycling ethanol, adding hydrochloric acid makes acid content reach 5mol/L, hydrolysis 3 hours, hydrolyzed solution hydro-oxidation sodium is regulated pH to 7.0, concentrates, dry, with the dry thing of dehydrated alcohol reflux, extract,, reclaim ethanol, drying under reduced pressure gets Cortex Araliae Elatae Radicis total sapogenins 136g, add chitosan 10g, poloxamer 20g, and adding Polyethylene Glycol 6000 to 400g, heating and melting drips and makes drop pill.
Claims (18)
1, a kind of is the oral drugs of active component with the Cortex Araliae Elatae Radicis total sapogenins.
2, medicine according to claim 1 is characterized in that can having only Cortex Araliae Elatae Radicis total sapogenins in the described active component, also can be that Cortex Araliae Elatae Radicis total sapogenins and other drug composition are united use.
3, medicine according to claim 2 is characterized in that described Cortex Araliae Elatae Radicis total sapogenins obtains by hydrolysis Aralia mandshurica total saponins.
4, medicine according to claim 3 is characterized in that method for hydrolysis is acid hydrolysis, enzyme hydrolysis or microbial hydrolysis.
5, according to each described medicine in the claim 1 to 4, it is characterized in that acceptable auxiliary is used on active constituents of medicine and the pharmaceutics.
6, medicine according to claim 5 is characterized in that containing in the adjuvant bio-adhesive agent and wetting agent.
7, medicine according to claim 6 is characterized in that also can containing dispersant in the adjuvant.
8, medicine according to claim 7 is characterized in that bio-adhesive agent in the adjuvant is meant any or the compositions more than two kinds in chitosan, carbomer, the polyvinylpyrrolidone; Wetting agent is meant lecithin and/or poloxamer; Dispersant is meant any or the compositions more than two kinds in micropowder silica gel, cyclodextrin, the Polyethylene Glycol.
9, medicine according to claim 8 is characterized in that the medicine proportion of composing is:
Active component 20～60%,
Bio-adhesive agent 1～10%,
Wetting agent 5～20%,
Dispersant 0～30%,
Other adjuvants 0～50%.
10, medicine according to claim 9 is characterized in that being made into tablet, capsule, granule or pill.
11, medicine according to claim 5 is characterized in that containing in the adjuvant wetting agent and dispersant.
12, medicine according to claim 11 is characterized in that also can containing the bio-adhesive agent in the adjuvant.
13, medicine according to claim 12 is characterized in that the bio-adhesive agent in the adjuvant is meant chitosan and/or carbomer; Wetting agent is meant any or the compositions more than two kinds in propylene glycol, lecithin, the poloxamer; Dispersant is meant Polyethylene Glycol or vegetable oil.
14, medicine according to claim 13 is characterized in that the medicine proportion of composing is:
Active component 10～40%,
Bio-adhesive agent 0～10%,
Wetting agent 5～20%,
Dispersant 50～80%,
Other adjuvants 0～20%.
15, medicine according to claim 14 is characterized in that being made into soft capsule, liquid hard capsule or drop pill.
16, the method for preparing each described medicine in the claim 6 to 15, it is characterized in that behind active constituents of medicine and any method mix homogeneously during required adjuvant mixes by fusion, dissolving, stirring, grinding or micronizing, add required conventional formulation adjuvant again, technology is made preparation routinely.
17, preparation method according to claim 16 is characterized in that using the vibromill superfine grinding method to mix.
18, in the claim 1 to 4 each described medicine be used for easing pain in preparation, antiinflammatory, antitumor, defying age, the application that protects the liver, transfer the medicine of blood fat or treatment diabetes.
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| CN200810101725A CN101530440A (en) | 2008-03-11 | 2008-03-11 | Oral pharmaceutical preparation of aralia elata total sapogenin and preparation method and application thereof |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104306387B (en) * | 2014-09-26 | 2018-06-12 | 中国医学科学院药用植物研究所 | Elatoside C are being prepared for treating and preventing the application in ischemic heart medicine |
| RU2665163C1 (en) * | 2017-12-15 | 2018-08-28 | Федеральное государственное бюджетное образовательное учреждение высшего образования "Самарский государственный медицинский университет" Министерства здравоохранения Российской Федерации | Aralia elata restorative drink syrup |
-
2008
- 2008-03-11 CN CN200810101725A patent/CN101530440A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104306387B (en) * | 2014-09-26 | 2018-06-12 | 中国医学科学院药用植物研究所 | Elatoside C are being prepared for treating and preventing the application in ischemic heart medicine |
| RU2665163C1 (en) * | 2017-12-15 | 2018-08-28 | Федеральное государственное бюджетное образовательное учреждение высшего образования "Самарский государственный медицинский университет" Министерства здравоохранения Российской Федерации | Aralia elata restorative drink syrup |
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Open date: 20090916 |